FDA Approves First Targeted Therapy Adakveo (crizanlizumab) by Novartis for Sickle Cell Disease to Reduce Vaso-Occlusive Crises

On November 16, Novartis announced that the U.S. FDA had approved its potential blockbuster therapy, Adakveo (crizanlizumab, also known as SEG101), for reducing the frequency of vaso-occlusive crises (VOC) in patients aged 16 years and older with sickle cell disease (SCD). This marks the first targeted therapy approved by the FDA for the treatment of VOC. Adakveo is a monoclonal antibody targeting P-selectin. The FDA’s approval came nearly two months ahead of schedule. This is the third innovative therapy approved by the FDA within two days, following BeiGene’s anticancer drug Brukinsa and Shionogi’s antibiotic Fetroja.

Sickle cell disease (SCD) is caused by mutations in the gene encoding the beta-globin subunit of hemoglobin (Hb). In the deoxygenated state, abnormal Hb polymerizes, causing red blood cells (RBCs) to assume a sickle shape and become rigid. These sickled RBCs obstruct capillaries and small vessels, leading not only to ischemic organ damage but also to pain. Pain episodes often begin abruptly, can affect any part of the body, and may last from several hours to days. Vaso-occlusive crises (VOC) are among the most common reasons for emergency department visits and hospitalizations in patients with SCD, resulting in reduced quality of life and increased risk of mortality. To date, therapeutic options for VOC remain very limited. Therefore, there is an urgent need for effective therapies to help patients with SCD prevent the suffering associated with VOC.

Adakveo is a monoclonal antibody targeting P-selectin. P-selectin is an adhesion molecule found on vascular endothelial cells and platelets, facilitating intercellular interactions (including those involving endothelial cells, platelets, red blood cells [RBCs], sickle RBCs, and white blood cells), thereby leading to multicellular adhesion and aggregation that can obstruct blood vessels. By binding to P-selectin, Adakveo prevents the occurrence of vaso-occlusive crises (VOC). Previously, it received Breakthrough Therapy Designation, Orphan Drug Designation, and Priority Review designation from the U.S. Food and Drug Administration (FDA).

This approval was based on the results of a randomized clinical trial involving 198 patients with sickle cell disease (SCD) and a history of vaso-occlusive crises (VOC). The trial results showed that patients treated with Adakveo had an annualized rate of 1.63 VOC events requiring treatment, representing a 45% reduction compared to the control group (2.98 events; p=0.010). Furthermore, 36% of patients receiving Adakveo remained free from any VOC during the clinical trial, and Adakveo delayed the time to first VOC after treatment initiation from 1.4 months to 4.1 months.

“Patients with sickle cell disease often face unique challenges, having silently endured unimaginable pain crises for a long time,” said Mr. Beverley Francis-Gibson, President and Chief Executive Officer of the Sickle Cell Disease Association of America. “We are delighted to have a new medication that can help thousands of patients with sickle cell disease reduce these dangerous and painful disease episodes.”

References:

[1] FDA approves first targeted therapy to treat patients with painful complication of sickle cell disease. Retrieved November 15, 2019, from https://www.prnewswire.com/news-releases/fda-approves-first-targeted-therapy-to-treat-patients-with-painful-complication-of-sickle-cell-disease-300959347.html

[2] New Novartis medicine Adakveo® (crizanlizumab) approved by FDA to reduce frequency of pain crises in individuals living with sickle cell disease. Retrieved November 15, 2019, from http://www.globenewswire.com/news-release/2019/11/15/1948216/0/en/New-Novartis-medicine-Adakveo-crizanlizumab-approved-by-FDA-to-reduce-frequency-of-pain-crises-in-individuals-living-with-sickle-cell-disease.html

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